Bottom Line:
The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals.However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage.Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional.

Affiliation: Department of Microbiology, University of Minnesota, Minneapolis, MN, United States of America.

ABSTRACTThe commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage.

pone.0153165.g001: Differentially expressed host genes in response to differing doses of C. albicans.VENN diagram of genes differentially expressed in epithelial cells in response to a low and a high dose of C. albicans.

Mentions:
The high dose of C. albicans elicited a greater transcriptional response from the epithelial cells than the low dose of C. albicans. However, we were surprised to find that only ~25% (21/90) of the genes differentially expressed in response to the low dose of C. albicans were also differentially expressed in response to a high dose of C. albicans (Table 2). Of these 21 genes, 14 genes were induced > 2 fold and one gene, F5, was repressed > 2 fold in response to the high dose of C. albicans compared to a low dose of C. albicans (Table 2). One possibile explanation for these results is that they are due to weak induction under one condition that is not apparent in the other condition. However, three genes (SLC26A3, MFAP5, and TACR1) are induced > 5 fold in response to a low dose, but are not observed among the genes induced in response to a high dose of C. albicans. In fact using a > 3 fold change in gene expression revealed that of nine genes differentially expressed in epithelial cells in response to a low dose of C. albicans, only four genes were also differentially expressed in response to a high dose of C. albicans (Fig 1). These results demonstrate that while 21 host genes show potential dose-dependent expression, many of the observed transcriptional responses are not readily explained by a dose-dependent model.

pone.0153165.g001: Differentially expressed host genes in response to differing doses of C. albicans.VENN diagram of genes differentially expressed in epithelial cells in response to a low and a high dose of C. albicans.

Mentions:
The high dose of C. albicans elicited a greater transcriptional response from the epithelial cells than the low dose of C. albicans. However, we were surprised to find that only ~25% (21/90) of the genes differentially expressed in response to the low dose of C. albicans were also differentially expressed in response to a high dose of C. albicans (Table 2). Of these 21 genes, 14 genes were induced > 2 fold and one gene, F5, was repressed > 2 fold in response to the high dose of C. albicans compared to a low dose of C. albicans (Table 2). One possibile explanation for these results is that they are due to weak induction under one condition that is not apparent in the other condition. However, three genes (SLC26A3, MFAP5, and TACR1) are induced > 5 fold in response to a low dose, but are not observed among the genes induced in response to a high dose of C. albicans. In fact using a > 3 fold change in gene expression revealed that of nine genes differentially expressed in epithelial cells in response to a low dose of C. albicans, only four genes were also differentially expressed in response to a high dose of C. albicans (Fig 1). These results demonstrate that while 21 host genes show potential dose-dependent expression, many of the observed transcriptional responses are not readily explained by a dose-dependent model.

Bottom Line:
The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals.However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage.Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional.

Affiliation:
Department of Microbiology, University of Minnesota, Minneapolis, MN, United States of America.

ABSTRACTThe commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage.